Investigating the Pleiotropic Role of KIF21B in Schizophrenia and Multiple Sclerosis: A Bioinformatics Analysis

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Abstract
Genome-wide association studies have identified shared genetic risk loci between schizophrenia (SCZ) and multiple sclerosis (MS), suggesting overlapping biological mechanisms despite distinct clinical presentations. Here, we aimed to characterize the biological plausibility of KIF21B as a shared genetic risk gene for SCZ and MS, two disorders with overlapping genetic risk loci despite distinct clinical presentations. We performed bioinformatics analyses of KIF21B using publicly available data from GTEx, STRING, and the GWAS Catalog, including tissue-specific expression profiling, protein interaction network analysis, transcriptome-wide co-expression analysis, and phenome-wide association analysis. KIF21B expression was significantly enriched in both brain and immune tissues compared to other tissue types. Protein interaction network analysis demonstrated that KIF21B functions within microtubule-based transport machinery essential for axonal function. Co-expression analysis identified significant correlation with immune-related genes, including the established MS susceptibility gene ANKRD55, with pathway enrichment for T cell activation and lymphocyte diferentiation. Phenome-wide association analysis confirmed KIF21B pleiotropy across multiple autoimmune and psychiatric conditions. These findings support KIF21B as a biologically plausible shared risk gene whose dual neural and immune functions may contribute to susceptibility for both neuropsychiatric and autoimmune diseases of the central nervous system.

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